The present invention is a process for preparing 2-substituted-1,4-dihydropyridines, useful as cardiovascular agents.
U.S. Pat. No. 4,567,268 reports a pyridinium bromide perbromide and NBS as a bromine generator for use in a process to form an internal ester, i.e. lactone, such as tetrahydrofuro(3,4-b)pyridine from a 3,5-diester-1,4-dihydropyridine. However, surprisingly it is now found that a pyridinium bromide perbromide provides a regiospecific brominated intermediate, i.e. having a bromine containing substituent at the 2-position in a 1,4-dihydropyridine. The intermediate, thus, is further reacted with a nucleophile to provide a wide range of 2-substituted-1,4-dihydropyridines in high yields heretofore available only through a complex three part Hantzsch reaction having low yields of products requiring extensive chromatographic separation.
Additionally selected novel 2-substituted-1,4-dihydropyridines having calcium blocking activity are the present invention.